title: Liver transplantation with a strongly positive crossmatch: case study and literature review.
abstract: A positive crossmatch has been associated with increased risk in liver transplantation. To study the clinical significance of preformed donor-specific human leukocyte antigen antibodies (DSAs) in liver transplantation, we reviewed patients who underwent liver transplantation with a strongly positive flow cytometry crossmatch. DSAs were evaluated with a Luminex solid phase assay. The complement-fixing ability of DSAs was tested with a complement component 1q (C1q) assay. Using an assay correlation between complement-dependent cytotoxicity crossmatch, flow cytometry crossmatch, and DSA results, we reviewed the effects of DSAs on the outcomes of our patients as well as reported cases in the literature. Five of 69 liver recipients had a strongly positive crossmatch: 4 had a positive T cell crossmatch [median channel shift (MCS) = 383.5 ± 38.9], and 5 had a positive B cell crossmatch (MCS = 408.8 ± 52.3). The DSAs were class I only in 1 patient, class I and II in 3 patients, and class II only in 1 patient. Cholestasis, acute rejection, or both were observed in 3 of the 4 patients with a positive T cell crossmatch with an MCS approximately greater than 300. The C1q assay was positive for 3 patients. Two had either persistent cholestasis or early acute rejection. One patient who was treated with preemptive intravenous immunoglobulin had an unremarkable outcome despite a positive C1q result. One of the 2 patients with a negative C1q assay experienced persistent cholestasis and early and recurrent acute rejection; the other had an unremarkable outcome. None of the patients died or lost a graft within the first year of transplantation. Our study suggests that human leukocyte antigen antibody screening, flow cytometry crossmatch MCS levels, DSA mean fluorescent intensity levels, and C1q assays may be useful in assessing the risk of antibody-mediated rejection and timely interventions in liver transplantation.
authors.affiliation: Division of Transplantation, Department of Surgery, Penn State University College of Medicine, Hershey, PA.
authors.forename: Garrett R
authors.initials: GR
authors.lastname: Leonard
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shike
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Uemura
authors.forename: Justine L
authors.initials: JL
authors.lastname: Gaspari
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Ruggiero
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Shah
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Riley
authors.forename: Zakiyah
authors.initials: Z
authors.lastname: Kadry
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D002779:Cholestasis / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D005234:Fatty Liver / Q000628:therapy; D005260:Female; D005355:Fibrosis / Q000628:therapy; D005434:Flow Cytometry; D006084:Graft Rejection; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000628:therapy; D008105:Liver Cirrhosis, Biliary / Q000628:therapy; D017093:Liver Failure / Q000276:immunology* / Q000628:therapy*; D016031:Liver Transplantation / Q000379:methods*; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012306:Risk; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000150:complications; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D015922:Complement C1q